Tertiary-aminoalkyl 4-amino-2-alkoxybenzoates and their synth esis



Patented Sept. 14, 1954 UNITED STATES PATENT OFFICE TERTIARY-AMINOALKYL4-AMINO-2-ALK- OXYBENZOATES AND THEIR SYNTHESIS Raymond 0. Clinton,Rensselaer, and Stanley C.

Laskowski, Menands, N. Y., assignors to Sterling Drug Inc., New York, N.Y., a corporation of Delaware No Drawing. Application June 17, 1950,Serial No. 168,843

where R" is a lower alkyl radical having 26 carbon atoms, X is a loweralkylene radical having 2-4 carbon atoms and NRR' is a loweraliphatic-like tertiary-amino radical. These esters, preferably in theform of their water-soluble acidaddition salts, have been found topossess outstanding local anesthetic properties.

In the above general formula, the lower alkyl radical represented by R"has 2-6 carbon atoms, including such examples as ethyl, n-propyl,isobutyl, Z-butyl, 3-amyl, n-heXyl and the like. The lower alkyleneradical designated hereinabove as X has 2-4 carbon atoms and has its twofree valence bonds on different carbon atoms. Thus, X includes suchexamples as CH2CH2-,

-CH2CH2CH2- -CHz( lH(CH5) -CH2CI-I2CH2CH2, -CH2CH(CH3),CH2-, and

the like. The lower aliphatic-like tertiary-amino radical shown above asNRR. comprehends lower dialkylamino radicals where R and R are loweralkyl groups, alike or difierent, and each alkyl group having preferablyl-6 carbon atoms, such dialkylamino radicals including dimethylamino,diethylamino, ethylmethylamino, diisopropylamino, di-n-butylamino,di-n-hexylamino and the like. Further, the lower aliphatic-liketertiary-amino radical designated as NRR' encompasses those radicalswhere R and R are joined directly or through an oxygen atom to formsaturated N-heteromonocyclic radicals having 5-6 ring atoms, illustratedby examples such as 1- piperidyl, Z-methyl-l-piperidyl,3-ethyl-1-piperidyl, l -methyl-bpiperidyl, 2,6-dimethyl-1-piperidyl,l-pyrrolidyl, 2-methyl-lpyrrolidyl, 2,5-di methyl-l-pyrrolidyl, lmorpholinyl, and the like.

The basic esters of our invention are conveniently prepared from4-nitro-2-hydroxybenzoic acid as illustrated by the following series ofre- 2 actions wherein R", X and NRR have the meanings given hereinabove:

N02 N02 ITTO:

I II

OH OR" OR GOOH COOR" OOOH lIII NH: N02

OR" OR" Thus, in step I 4-nitro-2-hydroxybenzoic acid is converted intoa lower alkyl 4-nitrc-2-alkoxybenzoate (A). In step II the lower alkyl4-nitro-2- alkoxybenzoate is saponified to yield the corresponding4-nitro-2-alkoxy-benzoic acid (B), which in step III is esterified toproduce the corresponding tertiary-aminoalkyl 4nitro-2-alkoxybenzoate(G). Then, in step IV the basic nitro ester (C) is reduced to thecorresponding tertiary-aminoalkyl 4-amino-2-alkoxybenzoate (D). Aspecific illustration of this series of reactions is the formation of2-dimethylaminoethyl 4- amino-2-ethoxybenzoate by converting l-nitro-2-hydroxybenzoic acid into ethyl4-nitro-2-ethoxybenzoate, saponifyingthis ester to produce l-nitro-2-ethoxybenzoic acid, esterifying thisacid to form Z-dimethylaminoethyl l-nitro-Z-ethoxybenzoate and reducingthe nitro group of said basic ester to form the correspondingZ-dimethylaminoethyl 4-amino-2-ethoxybenzoate. In practicing ourinvention we preferably carried out step I by reacting4-nitro2hydroxybenzoic acid with an alkyl benzenesulfonate and potassiumcarbonate in refluxing xylene. We carried out esteriiication step III bytwo difierent procedures: in one, the 4-nitro-2-alkoxybenzoic acid wasreacted with a tertiary-aminoalkyl halide; and in the other procedure,the 4-nitro-2-alkoxybenzoic acid was first converted into thecorresponding acid chloride which in turn was treated with atertiary-aminoalkanol. III also can be carried out by directly reactingthe 4-nitro-2-alkoxybenzoic acid with a tertiary aminoalkanol in thepresence of a suitable esteri The esterification step fication catalystsuch as dry hydrogen chloride. An alternative method of obtaining thebasic nitro ester (C) is by transesterifying the alkyl nitro ester (A)with a tertiary-aminoalkanol and re moving from the reaction mixture theformed alkanol, ROH. The reduction step IV was carried out both bychemical methods and by catalytic hydrogenation. Suitable chemicalreducing agents include iron and hydrochloric acid, ferrous sulfate andammonia, tin and hydrochloric acid, sodium hydrosulfite, etc. Inpracticing our invention, we preferably used iron and hydrochloric acid.Catalysts suitable when catalytic hydrogenation is employed includeRaney nickel, platinum, palladium, or other catalysts generallyeffective to catalyze hydrogenation of nitro groups to amino groups.

The tertiary-aminoalkyl esters of our invention are therapeuticallyactive whether employed as the free bases or as their salts withrelatively nontoxic organic or inorganic acids. In practicing ourinvention we found it convenient to isolate the basic esters as theirphosphates or hydrochlorides. However, other acid-addition salts arewithin the scope of our invention. Such additional salts include thehydrobromides, sulfates. citrates, sulfamates, tartrates, succinates,acetates, benzoates, oleates, and the like.

Specific embodiments of our invention are illustrated in the followingparagraphs.

(A) Alkyl 4-nitro-2-alkozcybenz0ates The preparation of these alkylesters is illustrated by the following preparation of ethyl 4-nitro-2-ethoxybenzoate: A stired mixture of 73.7 ofl-nitro-Z-hydroxybenzoic acid, 118.0 g. of anhydrous potassium carbonateand 178.8 g. of ethyl benzenesulfonate in 2 liters of xylene wasrefluxed under a continuous water separator for nineteen hours. Theinsoluble potassium salts were filtered oif and washed with hot drytoluene. The combined filtrate and washings were distilled under reducedpressure to remove the solvents, thereby leaving a residual oil whichsolidifled on cooling. from methanol, yielding ethyl4-nitro-2-ethoxybenzoate as cottony yellow needles, M. P. 53.9- 5 lfi C.(corn) yield 93%. Also prepared by the above procedure, each in yieldsof greater than 95% were the following: n-propyl4-nit1'o-2-npropoxybenzoate, oil; n-butyl 4-nitro-2-n-butoxybenzoate,oil; isobutyl 4-nitro-2-isobutoxybenzoate, oil; and n-hexyl4-nitro-2-n-hexoxybenzoate, oil.

imilar results were obtained when in the above procedure thecorresponding, but more expensive, alkyl toluenesulfonates were used asalkylating agents in place of the alkyl bengenesulfonates.

Alkyl 4-nitro-2-all oxybenzoates where in the two allcyl groups (esterand ether) differ can be prepared by alkylating an alkyl4-nitro-2-hydroxybenzoates. Such a procedure is illustrated by thefollowing preparation of methyl -nitro- Z-n-propoxybenzoate: A mixtureof 19.7 g. of methyl 4-nitro-2-hydroxybenzoate, 15.2 g. of am hydrouspotassium carbonate, 24 g. of n-propyl benzenesulfonate and 500 ml. ofxylene was refluxed with stirring under a continuous water separator forfifty-four hours. mixture was processed according to the foregoingexample to give a 95% yield of methyl 4-nitro- 2-n-propoxybenzoate, M.P. 42.343.9 C. (corr.). In a similar manner, using the appropriate alkyl4-nitro-2hydroxybenzoate and the appropriate alkyl benzenesulfonate, thefollowing esters were The solid was recrystallized 4 The resultingobtained: methyl 4-nitro-2-n-butoxybenzoate, an oil; and ethyl4-nitro-2-n-butoxybenzoate, M. P. 38.7-40.6 C. (corr.).

(B) 4-nz'tro-2-al7coa3yben2oic acids The preparation of these acids bysaponifying the above-described alkyl a-nitro-z-allcoxybenzoates (A) isillustrated by the following preparation of 4-nitro-2-ethoxybenzoicacid: The unrecrystallized ethyl 4-nitro-2-ethoxybenzoate obtained afterremoval of the solvents in the foregoing procedure (A) was dissolved in1600 ml. of aqueous ethanol. To this solution was added 2 to 3 molecularequivalents of sodium carbonate, and the resulting mixture was stirredunder reflux for sixteen hours. After the ethanol has been distilled offunder reduced pressure, the remaining aqueous solution was diluted withwater and made acidic with concentrated hydrochloric acid. Theprecipitated yellow solid was filtered, washed with water, dried in avacuum oven at C. and recrystallized from ethyl acetate. There was thusobtained a 98% yield of a-nitro-2-ethoxybenzoic acid as rosettes ofyellow needles, M. P. 147.3-l48.2 C. (corr.).

Additional i-nitro-2-all;oxybenzoic acids prepared according to theabove procedure include: 4 nitro 2 n propoxybenzoic acid, 94% yield, M.P. 1485-14946 C. (corn) 4-nitro-2-n-butoxybenzoic acid, 95.5% yield, M.P. 120.9122.8 C. (corn) 4 nitro 2 isobutoxybenzoic acid, 93% yield M. P.158.6159.6 C. (corn); and 4-nitro- 2-n-hexoxybenzoic acid, 94% yield, M.P. 86.3- 87.0 C. (corr.).

When the 4-nitro-2alkoxybenzoic acids were prepared from theunrecrystallized alkyl -nitro- 2-alkoxybenzoates, as in the aboveprocedure, there was present a very small amount of brown resinousmaterial, insoluble in ethyl acetate, benzene and related non-polarsolvents. We found that it was not necessary to remove this impurity insuccessfully carrying out our invention. However, said impurity wasreadily removed by dissolving the -nitro-2-alkoxybenzoic acid in ethylacetate, filtering off the impurity, and cooling the filtrate toprecipitate said acid. To insure complete precipitation, n-hexane wasadded to the mixture. Said brown impurity was not present when the4-nitro-2-allroxybenzoic acids were prepared from the recrystallizedalkyl 4-nitro-2- alkoxybenzoates in the above manner.

(C) Tertiary-aminoallcyl 41titro-2-al7co:rybenzoates Thesetertiary-aminoalkyl esters were prepared by esterifying the4-nitro-2-a1koxybenzoio acids described above. In practicing ourinvention we prepared these basic esters by two procedures: one, byreacting a tertiary-aminoalkyl halide with a 4-nitro-2-alkoxybenzoicacid in an appropriate solvent; and the other procedure, by reacting aQ-nitro-Z-alkoxybenzoyl halide with a tertiaryaminoalkanol. The formeralternative is illustrated by the following syntheses of3-(l-piperidyl)propyl 4-nitro-2-ethoxybenzoate and 2- dimethylaminoethyli-nitro 2 n butoxybenzoate.

3 (1 piperidybpropyl -nitro-Z-cthorybenzoate.-A stirred mixture of .2.2g. of 4-nitro-2- ethoxybenzoic acid and 38.8 g. of 3-(1'pi.peridyl)propyl chloride in 500 ml. of isopropanol was refluxed for twenty-fourhours. (The addition of a small amount of potassium or sodium iodidedecreases the reaction time necessary to about ten to fifteen hours.)The solvent was removed by distilling in vacuo and the remaining mobilebrown oil was poured into a 2 liter beaker and diluted with absoluteether to a volume of about 1.5 liters. The precipitated pale yellowsolid was filtered and washed with absolute ether. This solid was thendissolved in water, the solution made basic to litmus with sodiumhydroxide solution and the liberated basic ester extracted with ethylacetate. To insure complete extraction of the basic ester, sodiumchloride was added to the aqueous solution and the resulting mixture wasextracted further with ethyl acetate. The combined extracts were driedover anhydrous cal.- cium sulfate. After removal of the solvent bydistilling in vacuo, there remained g. (97%) of 3 (1 piperidyl) propyl4-nitro-2-ethoxybenzoate as a viscous brown oil. A portion of this basicester was converted into the monohydrochloride salt by dissolving it inbenzene and adding to the resulting solution an excess of anhydrousether containing 20% by weight of anhydrous hydrogen chloride. Theresulting oil was separated from the supernatant liquid by decantation,and was then dissolved in isopropanol. The isopropanol solution wasslowly diluted with n-hexane to turbidity. The separated yellow salt wasrecrytsallized from isopropanol and ethanolic hydrogen chloride,yielding as yellow needles, 3-(1-piperidyl) propyl4-nitro-2-ethoxybenzoate hydrochloride, which, after being filtered,washed with n-hexane and dried under 100 in vacuo, melted at 147-147.3C. (corn) Z-dimethylaminoethyl 4-nitro-2-n-butozcybenzoate.--A mixtureof 23.9 g. of 4-nitro-2-nbutoxybenzoic acid, 15.2 g. of anhydrouspotassium carbonate and 400 ml. of dry toluene was refluxed and stirredunder a continuous water separator. When the evolution of water hadceased (three hours), the water separator was removed and there wasadded 12.9 g. of dimethylaminoethyl chloride. The mixture was thenrefluxed with stirring for twenty hours, filtered while hot, and thesolvent was removed from the filtrate by distilling in vacuo. Theresidual oil was dissolved in dilute hydrochloric acid, the solution wasdecolorized with activated carbon and the base was liberated by theaddition of excess ammonia. The base was extracted with ethyl acetate,the solution was dried, and the ethyl acetate was removed bydistilling-in vacuo,

yielding 26.5 g. of (85.5%) 2-dimethylaminoethyll-nitro-2-n-butoxybenzoate as a pale yellow oil.

The other procedure we used in preparing the tertiary-aminoalkyll-ntiro-2alkoxybenzoates, or the reaction of a corresponding 4-nitro-2-alkoxybenzoyl halide with a tertiary-aminoalkanol, is illustrated by thefollowing preparation of Z-dimethylaminoethyl 4-nitro-2-ethoxybenzoatehydrochloride: To a cooled solution of 45.8 g. of4-nitro-2-ethoxybenzoyl chloride (prepared in quantitative yield byrefluxing a mixture of 42 g. of 4-nitro-2-ethoxybenzoic acid, 47.6 g. ofthionyl chloride and 125 ml. of dry benzene for two hours, evaporatingin vacuo, adding dry benzene andagain evaporating in vacuo) dissolved in250 ml. of dry benzene was added slowly 17.8 g. of2-dimethylaminoethanol dissolved in 100 ml. of dry benzene. The tanproduct began to crytsallize immediately. To insure more completeprecipitation of the product, the mixture was diluted with dry benzeneto a total volume of about 800 ml. After collecting the precipitate, themother liquor was concentrated in vacuo 6. thereby yielding a secondcrop. The combined precipitates were recrystallized, with decolorizationusing activated carbon, from isopropanol, thereby yielding as a paleyellow salt, Z-dimethylaminoethyl 4-nitro-2-ethoxybenzoatehydrochloride, which, after being dried at C. in vacuo, melted at140.5-141.2 C. (corn).

In the preparation of the acid chlorides where the 2-alkoxy substituentis higher than ethoxy (e. g., 4-nitro-2-n-butoxybenzoyl chloride), thereaction is run with pyridine as the hydrogen chloride acceptor toprevent cleavage of the alkoxy group. This procedure is illustrated asfollows: To 1 mole of acid and 1.2 mole of pure pyridine in 4 volumes ofdry benzene add 1.0 mole of thionyl chloride at 25 C., reflux one-halfhour, cool in ice, add with stirring 1.0 mole of the basic alcohol, mixwell. Remove solvent in vacuo and dissolve residue in water. Add excessammonium hydroxide and extract with toluene. Dry and remove toluene invacuo, add more toluene and again evaporate in vacuo (this is to removepyridine) leaving the pure base.

Additional tertiary-aminoalkyl Q-nitro-Z-al oxybenzoates, in the form oftheir hydrochlorides, prepared according to the above described pro--cedures are given in Table A.

NO5H0 is l-piperidyl.

Additional tertiary-aminoalkyl 4-nitro-2-alkoxybenzoates which can beprepared according to the procedures described hereinabove include thefollowing: 3-(l-pyrrolidyl)propyl 4-nitro-2- n-proproxybenzoate; 2(2,5-dimethyl-l-pyrrolidyl) ethyl 4 nitro-2-n-hexoxybenzoate; 4dimethylaminobutyl l-nitro-2n-butoxybenzoate; 2 (di n butylamino) ethyl4-nitro-2-(2-lp-ropoxy)benzoate; 2 diethylaminoethyl 4-nitro2-n-amoxybenzoate; 2 (3-ethyl-1-piperidyl) ethyl4-nitro-2-isobutoxybenzoate; 3-(2-methyl-l-pyr rolidyl) propyl4-nitro-2- (S-amoxy) benzoate; 3- dirnethylamino-Z-propyl4.nitro-2-n-butoxybe-nzoate; 2-(4-morpholinyDethyl4-nitro-2-n-hexoxybenzoate; and 2-(2-methyl1-piperidyl) ethyl4-nitro-2-ethoxybenzoate.

(D) Tertiary-aminoallcyl 4-amz'no-2-al7cozry- Y benzoates Exemplary ofthe preferred procedure for preparing these basic esters is thefollowing prepa ration of 3 (l-piperidyDpropyl 4-amino 2 ethoxybenzoate:To a hot stirred mixture of 49.9

g. of powdered iron, 1 ml. of concentrated 'hydrochloric acid and 500ml. of 80% ethanol was added slowly 50.0 g. of 3-(l-piperidyl)propyl 4-nitro-2-ethoxybenzoate over a period of about ten minutes. The resultantbrown-colored solution was heated with stirring for another thirtyminutes, after which time g. of sodium bicarbonate was added. Themixture was stirred an additional ten minutes and then filtered througha filter aid which was washed with hot ethanol. The combined filtrateand washings were concentrated by distilling in vacuo, cooled andextracted with ethyl acetate. The combined extracts were dried overanhydrous potassium carbonate and the solvent removed by distilling invacuo. The pale orange crystalline residue was recrystallized from ethylacetate-n-hexane and dried at 60 C. thereby yielding 42 g. (91%) of 3-(l-piperidyDpropyl 4: amino-Z-ethoxybenzoate, M. P. 90.0-90.8" C.(corn). The dihyrochloride salt of this basic ester was prepared bydissolving a portion of said basic ester in dry benzene and adding anexcess of anhydrous ether containing by weight of anhydrous hydrogenchloride. The gummy precipitate was separated from the supernatantliquid by decanting, and was dissolved in isopropanol. When cooled, theisopropanol solution yielded a white precipitate. Recrystallization ofthis precipitate from absolute ethanol yielded, in the form of whiteneedles, 3- (l piperidyDpropyl 4-amino-2-ethoxybenzoate dihydrochloride,M. P. 171.6-l'76.6 C. (corn). Alternatively, the phosphate may beprepared by treating a solution of the base in absolute alcohol with anequivalent amount of 85% phosphoric acid, filtering the precipitatedphosphate and recrystallizing the same from dilute ethanol.

The above reduction of the tertiary-aminoalkyl e-nitro-Z-alkoxybenzoatesto yield the corresponding 4-amino esters can be carried out bycatalytic hydrogenation as illustrated by the following generalpreparations: Ten grams of the tertiary-aminoalkyl 4-nitro-2-alloxybenzoate in 150 ml. of ethanol is hydrogenated using 50 lbs. pressureof hydrogen at C. in the presence of 2 g. of Raney nickel. After therapid exothermic reaction, the catalyst is filtered oil and the filtrateevaporated to dryness. The resulting residue is dissolved in benzene andhydrogen chloride is added as above. Alternatively, other catalysts canbe employed as exemplified in the following use of platinum: Fifteengrams of tertiaryaminoalkyl 4-nitro-2-alkoxybenzoate in 150 ml. ofethanol is reduced at 25 lbs. pressure of hydrogen at 25 C. in thepresence of 200 mg. of platinum oxide monohydrate and 5 ml, ofconcentrated hydrochloric acid. After the rapid exothermic reaction, thecatalyst is filtered oil and the filtrate distilled in vacuo to removethe alcohol. The residue is taken up in water and potassium carbonate isadded to the resulting solution to liberate the basic ester, which isextracted with benzene. The benzene extract is dried and treated withexcess hydrogen chloride above to give the tertiary-aminoalkyl e-amino-Z-alkoxybenzoate dihydrochloride.

The preparation of monohydrochlorides of the tertiary-aminoalkyl4-amino-2-alkoxybenzoates exemplified by the following description: To asolution of 70.0 g. of pure Z-diethylaminoethyl4.-amino-2-n-propoxybenzoate in 600 ml. of ethyl acetate was added anexcess of 20% ethereal hydrogen chloride. After mixing well, thesupernatant liquid was decanted from the precipitated thick gum, and thegum was washed by successive trituration with 200 m1. of absolute etherand 300 ml. of warm ethyl acetate. The gum was dissolved in 300 m1. ofabsolute alcohol, and to the solution was added 78.0 g. of pure2-diethylaminoethyl 4-amino-2-n-propoxybenzoate. The clear solution wasslowly diluted to two liters with ethyl acetate and the crystallineprecipitate was collected and Washed with ethyl acetate. The product wasrecrystallized by dissolution in a mixture of 300 ml. of absolutealcohol and 400 ml. of isopropyl alcohol, decolorization with activatedcharcoal, and dilution while warm with one liter of ethyl acetate andone liter of absolute ether. 2 diethylaminoethyl4-amino-2-n-propoxybenzoate monohydrochloride crystallized in largewhite prisms, M. P. 148.3-150.0 C. (corn). The yield was 126 grams.

Alternatively, the pure base is dissolved in absolute alcohol, analiquot portion is titrated with standard acid, and the calculatedamount of a standard solution of hydrogen chloride in absolute alcoholis added. The monohydrochloride is precipitated by the addition ofexcess absolute ether and recrystallized as outlined above.

Additional tertiary-aminoalkyl 4 amino-2- alkoxybenzoates, in the formof their phosphates or hydrochlorides, prepared according to the aboveprocedures are given in Table B.

TABLE B n R NRR M. P./ C. (corn) N(CH2)2.... 70. 2-77. 1 N(C2H )2. 151.8-152. 8' N CH. 1570-1600 c N(C2H5)2 1328-13 18 NC H t." 169.4-1721) KN(CH3)2. 1508-1590 a N(C2H;)z 125.4-126/1 NCtHio 80. 0-83. 0 N(C:I-L)2148. 13-150. 9 N(C H )z. 154. 9-155. 3 N(C H z. 152. 5-154. 5 U (CzHs 2128. 6-129. 6 (31.1110 2. 178. 7-170. 8 0 N(CzH5)2 130.5l33.5 NC5H10133. 2 c

* NC H1o=l-piperidyl. b M. P. of base. a Dihydrochloride. d M. P. ofbase is 62.864.0 0. (corn). B Monohydrochloride.

l M. P. of base is 92.0-93.8 0. (com). 2 With decomposition.

Additional tertiary-aminoalkyl 4-amino-2-alkoxybenzoates which can beprepared according to the procedures described hereinabove include thefollowing: 3-(l-pyrrolidyl) propyl i-amino-Z- n-propoxybenzoate;2-(2,5-dimethyl-l-pyrrolidyDethyl 4-amino-2-n-hexoxybenzoate;l--dimethylaminobutyl 4-amino-2-n-butoxybenzoate; 2-(di-n-butylamino)ethyl 4-amino-2 (2. pro poxy)benzoate; 2-diethylaminoethyl i-amino-Z-n-amoxybenzoate; 2- (3-ethyl-1-piperidyl) ethylll-amino-2-isobutoxybenzoate; 3-(2-methyl 1 pyrrolidyl) propyl 4 amino 2(3 amoxy) benzoate; 3-dimethyl-2-propyl 4-amino-2-n-butoxybenzoate;2-(4-morpholinyl)ethyl l-amino-Z-nhexoxybenzoate; and2-(2-methyl1--piperidyl) ethyl 4-amino-2-ethoxybenzoate.

9 We claim: 1. A member of the group consisting of a basic ester havingthe formula NHz where NRR is a tertiary-amino radical selected from thegroup consisting of lower dialkylamino, l-piperidyl, (lower alkylated)-1-piperidyl, 1- pyrrolidyl, (lower alkylated)-1pyrrolidyl and 4-morpholinyl, X is a lower alkylene radical having 2-4 carbon atoms andR" is a lower alkyl radical having 2-6 carbon atoms, and acid-additionsalts thereof.

2. An acid-addition salt of a basic ester having the formula ORII whereX is a lower alkylene radical having 2-4 carbon atoms and R" is a loweralkyl radical having 2-6 carbon atoms.

3. An acid-addition salt of a basic ester having the formula NHzOO--XNRR where R" is a lower alkyl radical having 2-6 carbon atoms, X isa lower alkylene radical having 2-4 carbon atoms and NRR' is al-piperidyl radical.

4. An acid-addition salt of a basic ester having the formula 10 where R"is a lower alkyl radical having 2-6 carbon atoms.

5. An acid-addition salt of a basic ester having the formula ReferencesCited in the file of this patent UNITED STATES PATENTS Number Name Date1,317,250 Wildman Sept. 30, 1919 2,288,334 Vliet June 30, 1942 2,376,860Blicke May 29, 1945 FOREIGN PATENTS Number Country Date 317,296 GreatBritain 1930 349,640 Great Britain 1931

1. A MEMBER OF THE GROUP CONSISTING OF A BASIC ESTER HAVING THE FORMULA 